Metabolism of apolipoprotein C-III in normolipemic human subjects

Malmendier, Claude; Lontie, Jean-Francois; Grutman, G.A.; Delcroix, Claude

doi:10.1016/0021-9150(88)90288-2

Cited by 30 publications

(18 citation statements)

References 26 publications

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“…These results suggest that the two kinetically distinct pools may be related to conformational changes in individual apoC-III molecules on the lipoprotein surface. In a separate study, labeled apoC-III disappearance from plasma was found to follow tri-exponential kinetics, and differences in plasma and urine radioactivity curves suggested the presence of kinetically distinct pools of apoC-III ( 30 ). These fi ndings for apoC-III are analogous to the properties of apoE, which is a fi xed and exchangeable component within VLDL of various sizes ( 31 ).…”

Section: Figmentioning

confidence: 84%

Complexities of plasma apolipoprotein C-III metabolism

Sacks

Zheng

Cohn

2011

Journal of Lipid Research

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Section: Figmentioning

confidence: 84%

Complexities of plasma apolipoprotein C-III metabolism

Sacks

Zheng

Cohn

2011

Journal of Lipid Research

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“…Compared with apoB and HDL apoA-I, few studies have examined the kinetics of apoC-III. Early apoC-III radiotracer studies supported the complete exchange of apoC-III between the VLDL and HDL fractions (74,75). Bukberg et al (76), using similar methodology, also observed rapid, but not complete, exchange of apoC-III between VLDL and HDL.…”

Section: Kinetic Studies In Humansmentioning

confidence: 93%

Thematic review series: Patient-Oriented Research. Design and analysis of lipoprotein tracer kinetics studies in humans

Barrett

Chan

Watts

2006

Journal of Lipid Research

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Lipoprotein tracer kinetics studies have for many years provided new and important knowledge of the metabolism of lipoproteins. Our understanding of kinetics defects in lipoprotein metabolism has resulted from the use of tracer kinetics studies and mathematical modeling. This review discusses all aspects of the performance of kinetics studies, including the development of hypotheses, experimental design, statistical considerations, tracer administration and sampling schedule, and the development of compartmental models for the interpretation of tracer data. In addition to providing insight into new metabolic pathways, such models provide quantitative information on the effect of interventions on lipoprotein metabolism. Compartment models are useful tools to describe experimental data but can also be used to aid in experimental design and hypothesis generation. The SAAM II program provides an easy-to-use interface with which to develop and test compartmental models against experimental models. The development of a model requires that certain checks be performed to ensure that the model describes the experimental data and that the model parameters can be estimated with precision.In addition to methodologic aspects, several compartment models of apoprotein and lipid metabolism are reviewed. Years of clinical investigation have provided valuable insight into the complexity of human lipoprotein metabolism. The measurement of plasma lipoprotein concentrations provides useful information, but from a functional viewpoint these concentrations reflect the balance between input and output in the lipoprotein system in plasma. The only way to quantify input and output in this system is by undertaking kinetics studies, typically using tracer methodology. These studies, however, are time-consuming and difficult to perform. Nevertheless, they are important to characterize the pathways that result in dyslipidemic states and to describe the in vivo mechanisms of action of treatments designed to regulate dyslipidemia and cardiovascular disease risk in clinical practice. There are many steps to consider when planning such metabolic studies. This review touches on all aspects of the design and analysis of lipoprotein kinetics studies, including philosophical angles, tracer methodology, mathematical modeling, and statistical considerations related to experimental design and analysis.With the advent of commercial stable isotopes and endogenous labeling protocols, some aspects of performing kinetics studies are now easier than when radioactive tracers and laborious exogenous labeling of lipoproteins were required. However, the number of laboratories and research groups undertaking these types of metabolic studies has changed little, highlighting the complexity of the methods involved.In addition to the design and modeling aspects of lipoprotein kinetics studies, what we have learned from apolipoprotein B (apoB) and HDL apoA-I and apoA-II tracer kinetics studies is covered in the present series of reviews by Parhofer and Barret...

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“…Early kinetic studies using radiolabeled apoC-III demonstrated exchange and equilibration of apoC-III between TRL and HDL particles in both normal and hyperlipidemic subjects ( 6,13,14 ). Furthermore, in vitro studies have demonstrated that the transfer of apoC-III between VLDL and HDL particles is bidirectional and that all of the apoC-III appears to be available for exchange such that equilibrium is acquired ( 15 ).…”

Section: Isolation and Measurement Of Isotopic Enrichment Of Apoc-iiimentioning

confidence: 99%

Plasma apolipoprotein C-III metabolism in patients with chronic kidney disease

Ooi

Chan

Watts

et al. 2011

Journal of Lipid Research

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Supplementary key words kinetics • lipoprotein metabolism • triglyceridesCardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD) ( 1 ). While the precise mechanisms for increased CVD risk are unknown, both traditional and novel CVD risk factors have been implicated ( 1, 2 ). Dyslipidemia, a well-established risk factor for CVD in the general population, is highly prevalent in CKD ( 3, 4 ). The most frequent dyslipoproteinemic phenotype patterns are elevated plasma concentrations of triglycerides and increased numbers of atherogenic triglyceride-rich lipoprotein (TRL) particles, particularly VLDL and intermediate-density lipoprotein (IDL) ( 3, 4 ). The regulation of TRL metabolism in CKD, however, is poorly understood.Apolipoprotein C-III (apoC-III) is an 8.8 kDa glycoprotein synthesized by the liver and intestines ( 5 ). ApoC-III is highly associated with hypertriglyceridemia and is a powerful independent predictor of CVD risk in subjects without renal disease ( 5 ). In the circulation, apoC-III is associated with TRL and HDL exchanging rapidly between these lipoproteins ( 6 ). In vitro studies demonstrate that apoC-III Abstract Moderate chronic kidney disease (CKD) (defi ned by an estimated glomerular fi ltration rate of 30-60 ml/min) is associated with mild hypertriglyceridemia related to delayed catabolism of triglyceride-rich lipoprotein particles. Altered apolipoprotein C-III (apoC-III) metabolism may contribute to dyslipidemia in CKD. To further characterize the dyslipidemia of CKD, we investigated the kinetics of plasma apoC-III in 7 nonobese, nondiabetic, non-nephrotic CKD subjects and 7 age-and sex-matched healthy controls, using deuterated leucine ([5, 5, 5, 2 H 3 ]leucine), gas chromatography-mass spectrometry, and multicompartmental modeling. Compared with controls, CKD subjects had higher concentrations of plasma and VLDL triglycerides and plasma and VLDL apoC-III ( P < 0.05). The increased plasma apoC-III concentration was associated with a decreased apoC-III fractional catabolic rate (FCR) (1.21 ± 0.15 vs. 0.74 ± 0.12 pools/day, P = 0.03). There were no differences between apoC-III production rates of controls and those of CKD subjects. In CKD subjects, plasma apoC-III concentration was signifi cantly and negatively correlated with apoC-III FCR ( r = ؊ 0.749, P = 0.05) but not with apoC-III production rate. Plasma apoC-III concentration was positively correlated with plasma and VLDL triglycerides and VLDL apoB concentrations and negatively correlated with VLDL apoB FCR ( P < 0.05 for all). ApoC-III FCR was negatively correlated with plasma and VLDL triglycerides and VLDL apoB concentration and positively correlated with VLDL apoB FCR ( P < 0.05 for all). Altered plasma apoC-III metabolism is a feature of dyslipidemia in moderate CKD. Modifi cation of apoC-III catabolism may be an important therapeutic target for reducing cardiovascular disease risk in moderate

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Metabolism of apolipoprotein C-III in normolipemic human subjects

Cited by 30 publications

References 26 publications

Complexities of plasma apolipoprotein C-III metabolism

Complexities of plasma apolipoprotein C-III metabolism

Thematic review series: Patient-Oriented Research. Design and analysis of lipoprotein tracer kinetics studies in humans

Plasma apolipoprotein C-III metabolism in patients with chronic kidney disease

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